ABSTRACT
Analysis of urinary captopril was necessary for dosage form bioavailability and dose titration studies. The necessity for long-term storage of samples prior to analysis and the presence of an oxidation-prone thiol of captopril required development of an acid-chelate stabilization method for urinary captopril. An electrochemical reduction released disulfide-conjugated captopril for thiol colorimetry. Of several rugged reduction cells evaluated, one with a porous glass disk separating the anode and the mercury pool cathode was preferred. Methylene chloride partitions from acidified salt-saturated urines, before and after reduction, allowed the measurement of free and disulfide-conjugated captopril. The drug partitioned into the solvent, whereas the aqueous phase retained acid protonated, amino group-bearing thiols like cystine. Subsequent solvent evaporation volatilized other potential colorimetric interferences. An automated thiol colorimetry of 25 samples/hr was developed for analysis of the aqueous reconstitutes. Results were confirmed by a subsequently developed HPLC method with electrochemical detection.
Subject(s)
Captopril/urine , Proline/analogs & derivatives , Colorimetry/methods , Disulfides/urine , Electrochemistry , Humans , Oxidation-Reduction , Solubility , Sulfhydryl CompoundsABSTRACT
A high-pressure liquid chromatographic assay was developed for the analysis of the beta-adrenergic blocking agent nadolol as a bulk material or formulated in a tablet. Other beta-adrenergic blocking drugs such as acebutolol, alprenolol, atenolol, metoprolol, oxprenolol, pindolol, practolol, propranolol, sotalol, and timolol can be chromatographed in this system. An ethylsilane column and a mobile phase consisting of 35% methanol-65% aqueous 0.0005 M hydrochloric acid-0.05 M sodium chloride are used. Detection is either at 254 nm with a variable-wavelength detector. As exemplified by nadolol, the drug content can be quantitated with or without atenolol as an internal standard.
